One-Pot Preparation of Alpha-Chymotrypsin Degradable Hydrogel Micropatterns for Controlled Drug Release

Abstract

Fluorouracil (5-FU) has been the most widely used chemotherapy agent since its clinical introduction in 1957, and it continues to form the basis of treatment for various cancers. However, due to the side effects of an antimetabolite, a strategy fulfilling stringent requirements placed on a 5-FU delivery system requires controlled and extended release of 5-FU in a localized manner. Here, an in-situ gel-forming method for the preparation of micropatterned, alpha-chymotrypsin-degradable hydrogel (PHcd) for controlled release of 5-FU is introduced. More specifically, methacrylated hyaluronic acid (HA) and polyethylene glycol diacrylate (PEGDA), known for their excellent moisture retention capacity, are chosen for skin therapy. They are crosslinked with CYKC peptide through a thiol-ene click reaction. The synthesis of the CYKC peptide and its cleavage by alpha-chymotrypsin were confirmed using high-performance liquid chromatography (HPLC). Additionally, the in vitro release behavior was accurately monitored using the micropatterning method, demonstrating the stable immobilization and successful sustained release of 5-FU upon the addition of alpha-chymotrypsin in micropatterned PHcd hydrogel. Consequently, this micropatterned PHcd hydrogel can be considered a promising scaffold for localized and sustained delivery of cytotoxic drugs for skin cancer treatment.